Urinary Albumin to Creatinine Ratio as Potential Biomarker for Cerebral Microvascular Disease

Abstract

Elevated urinary albumin to creatinine ratio (ACR) and white matter hyperintensity (WMH) volume seen on brain MRI are measures of microvascular disease which may have shared susceptibility to metabolic and vascular insults. We hypothesized that elevated ACR may be useful as inexpensive biomarker to predict presence of cerebral microvascular disease. We assessed the association between ACR at study entry and subsequent WMH volume. We evaluated pulse pressure, mean arterial pressure, hypertension duration, waist circumference, fasting glucose, glomerular filtration rate (GFR) and C-reactive protein (CRP) as potential mediators and diabetes as a moderator of the association between ACR and WMH. Data were collected at study entry and at follow-up approximately 7 years later in a multi-ethnic population sample of 1281 participants (mean age=51, SD=9.5) from Dallas County. Overall, ACR differences were only marginally (p= 0.05) associated with subsequent WMH. In mediator analysis, however, ACR differences related specifically to arterial pulsatility(β=0.010, bootstrap 95% Confidence Interval (CI): 0.002 to 0.021) and waist circumference (β= -0.004, bootstrap 95% CI: -0.011 to -0.001) were significantly associated with WMH. ACR differences related to serum glucose and CRP were not associated with WMH. ACR evaluated at the same time as WMH had a higher level of significance (p< 0.001) indicating greater utility in predicting current cerebrovascular insults.

Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese ― The Hisayama Study ―

“…Previous epidemiological studies have shown that elevated urinary albumin is associated with larger WMHV, [12][13][14][15][16] which is consistent with the findings of the present study. This study showed that increased urinary albumin, within variables were assessed by means of a cross-sectional design, we could not definitively establish causality among them.…”

“…Several cross-sectional observational studies conducted in Western countries have reported that elevated urinary albumin levels are significantly associated with larger WMH volumes, which were measured quantitatively by automatic techniques. [12][13][14][15] Only study has used automatic quantitative evaluation of WMH in Asian populations with different genetic and lifestyle backgrounds. 16 Moreover, several epidemiological studies have examined the association of albuminuria with WMH enlargement in general Asian populations.…”

Albuminuria and Cerebral Small Vessel Disease: A Systematic Review and Meta‐Analysis

“…A cross‐sectional study of 568 individuals with hypertension without a history of stroke found that 1 SD increase in ACR was associated with higher odds for deep and infratentorial CMBs (OR = 2.03, 95% CI = 1.41–4.31), but no association was found for lobar CMBs . A population‐based study found an association between baseline ACR and WMH volume after 7 years ( β = 0.039, P = .05) and a stronger association when ACR and WMH were concurrently assessed ( β = 0.073, P < .001). An analysis of the total burden of cerebral SVD (WMHs, LIs, CMBs, EPVSs) in 210 individuals with acute stroke found greater burden in subjects with proteinuria (OR = 2.15, 95% CI = 1.16–3.98) …”

Microangiopathy is associated with bone loss in female type 2 diabetes mellitus patients

“…6 The ocular fundus photographic changes and 24-h urine protein in T2DM patients might provide a clue of microangiopathy. [7][8][9][10] In this study, we sought to investigate the correlation between microangiopathy and BMD in postmenopausal women with T2DM and age-matched male patients using ocular fundus photographic changes and 24-h urine protein as surrogate microangiopathy markers.…”